Cyclooxygenase-2 Expression is Induced during Human Megakaryopoiesis and Characterizes Newly Formed Platelets

Cyclooxygenase (COX)-1 or -2 and prostaglandin (PG) synthases catalyze the formation of various PGs and thromboxane (TX) A2. We have investigated the expression and activity of COX-1 and -2 during human megakaryocytopoiesis. We analyzed megakaryocytes from bone marrow biopsies and derived from thrombopoietin-treated CD34+hemopoietic progenitor cells in culture. Platelets were obtained from healthy donors and patients with high platelet regeneration because of immune thrombocytopenia or peripheral blood stem cell transplantation. By immunocytochemistry, COX-1 was observed in CD34+cells and in megakaryocytes at each stage of maturation, whereas COX-2 was induced after 6 days of culture, and remained detectable in mature megakaryocytes. CD34+cells synthesized more PGE2than TXB2(214 ± 50 vs. 30 ± 10 pg/106cells), whereas the reverse was true in mature megakaryocytes (TXB28,440 ± 2,500 vs. PGE2906 ± 161 pg/106cells). By immunostaining, COX-2 was observed in